Authors: Aru Narendran Lucas Coppes Aarthi Jayanthan Michael Coppes Bijan Teja Delphine Bernoux David George Douglas Strother
Publish Date: 2008/07/24
Volume: 90, Issue: 2, Pages: 171-180
Abstract
Atypical teratoid/rhabdoid tumor AT/RT is a highly malignant central nervous system neoplasm that usually affects infants and young children In this report we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid CSF of an infant with AT/RT These cells retained the morphological and biomarker characteristics of the original tumor A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4 InsulinR PDGFR and IGFIR which appear to depend on Hsp90 to maintain their active form IGFIR activity is consistent with data from other established AT/RT cell lines Inhibition of IGFIR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells In addition neutralizing antibodies to IGFII also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells In addition to previously described cell lines and xenograft models continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumorThis work was supported in part by the Kids Cancer Care Foundation of Alberta KCCF for which the cell line was named Additional research funding was provided by the Brain Tumor Research Foundation of Canada We acknowledge the Oncology Pharmacy at the Alberta Children’s Hospital for providing many of the antineoplastic agents used in our experiments
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